Insertion of polar and nonpolar unsaturated molecules into carbon-rhenium bonds generated by C-H bond activation: Synthesis of phthalimidine and indene derivatives

Article abstract of DOI:10.1021/ja054216i

A rhenium complex, [ReBr(CO)₃(thf)]₂, catalyzes the reaction of an aromatic aldimine with an isocyanate and an acetylene to give a phthalimidine and an indene derivative in a quantitative yield, respectively. The reactions proceed vi

Full text of DOI:10.1021/ja054216i

Published on Web 12/14/2005
Insertion of Polar and Nonpolar Unsaturated Molecules into
Carbon-Rhenium Bonds Generated by C-H Bond Activation:
Synthesis of Phthalimidine and Indene Derivatives
Yoichiro Kuninobu,* Yukimi Tokunaga, Atsushi Kawata, and Kazuhiko Takai*
Contribution from the DiVision of Chemistry and Biochemistry, Graduate School of Natural
Science and Technology, Okayama UniVersity, Tsushima, Okayama 700-8530, Japan
Received June 26, 2005; E-mail: kuninobu@cc.okayama-u.ac.jp; ktakai@cc.okayama-u.ac.jp
Abstract: A rhenium complex, [ReBr(CO)3(thf)]2, catalyzes the reaction of an aromatic aldimine with an
isocyanate and an acetylene to give a phthalimidine and an indene derivative in a quantitative yield,
respectively. The reactions proceed via C-H bond activation, insertion of the isocyanate or the acetylene,
intramolecular nucleophilic cyclization to the aldimine of the generated amido- or alkenyl-rhenium species,
and reductive elimination. In contrast to ruthenium and rhodium catalysts, which are usually employed in
this type of reaction, the rhenium catalyst promotes the insertion of a polar unsaturated molecule. This
occurs more easily than the insertion of a nonpolar unsaturated molecule.
Introduction
derivatives via ortho-manganated aryl ketones generated by
treatment of aryl ketones with a stoichiometric amount of a
Transition-metal-catalyzed chemical transformations via C-H
bond activation are an important and challenging theme because
the introduction of functional groups can be achieved in short
reaction steps and byproducts such as metal halides are not
formed. Although there have been many examples of the
insertion of unsaturated bonds, such as olefins and acetylenes
to aromatic C-H bonds using ruthenium or rhodium complexes
as a catalyst,1 most have been limited to nonpolar unsaturated
bonds. Insertion of polar unsaturated bonds into carbon-metal
bonds generated by C-H bond activation could enlarge the
scope of the C-H bond activation; however, only a few
examples have been reported.2
manganese complex.5 Only a few reports have appeared on the
rhenium-catalyzed C-H bond activation.6,7 This is the first
rhenium-catalyzed insertion of an unsaturated molecule into a
C-H bond, and it is also the first intramolecular nucleophilic
addition of an organometallic species derived from C-H bond
activation to an imine moiety.
We disclose here the rhenium-catalyzed insertion of a
nonpolar molecule, acetylene, and more interestingly, a polar
molecule, isocyanate, into a carbon-rhenium bond at the ortho-
position of an aldimine, derived from catalytic C-H bond
activation, proceeds smoothly and that an indene8-11 or a
As one of the applications of C-H bond activation chemistry,
there have been several reports on the construction of cyclic
compounds.3 However, these reactions are limited to intramo-
lecular cyclizations and need special starting materials to afford
the cyclic products. In contrast, we have recently succeeded in
the rhenium-catalyzed intermolecular annulation of aromatic
aldimines with internal acetylenes via C-H bond activation to
give indene derivatives.4 The annulation method requires only
a catalytic amount of a rhenium complex, and compares
favorably with the manganese-mediated5a synthesis of indene
(5) For the synthesis of indene derivatives using transition metal compounds,
see: (a) Liebeskind, L. S.; Gasdaska, J. R.; McCallum, J. S. J. Org. Chem.
1989, 54, 669. (b) Semmelhack, M. F.; Ho, S.; Cohen, D.; Steigerwald,
M.; Lee, M. C.; Lee, G.; Gilbert, A. M.; Wulff, W. D.; Ball, R. G. J. Am.
Chem. Soc. 1994, 116, 7108. (c) Halterman, R. L.; Zhu, C. Tetrahedron
Lett. 1999, 40, 7445. (d) Romines, K. R.; Lovasz, K. D.; Mizsak, S. A.;
Morris, J. K.; Seest, E. P.; Han, F.; Tulinsky, J.; Judge, T. M.; Gammill,
R. B. J. Org. Chem. 1999, 64, 1733. (e) Xi, Z.; Guo, R.; Mito, S.; Yan, H.;
Kanno, K.-i.; Nakajima, K.; Takahashi, T. J. Org. Chem. 2003, 68, 1252.
(f) Ming-Yuan, L.; Madhushaw, R. J.; Liu, R.-S. J. Org. Chem. 2004, 69,
7700. (g) Chang, K.-J.; Rayabarapu, D. K.; Cheng, C.-H. J. Org. Chem.
2004, 69, 4781. (h) Lautens, M.; Marquardt, T. J. Org. Chem. 2004, 69,
4607.
(6) Jacob, J.; Espenson, J. H. Inorg. Chim. Acta 1998, 270, 55.
(7) An example of rhenium-catalyzed C(sp3)-H bond activation has been
reported: Chen, H.; Hartwig, J. F. Angew. Chem., Int. Ed. Engl. 1999, 38,
3391.
(8) For the building blocks for functional materials, see: (a) Akbulut, U.;
Khurshid, A.; Hacioglu, B.; Toppare, L. Polymer 1990, 31, 1343. (b)
Barbera, J.; Rakitin, O. A.; Ros, M. B.; Torroba, T. Angew. Chem., Int.
Ed. Engl. 1998, 37, 296. (c) Yang, J.; Lakshmikantham, M. V.; Cava, M.
P. J. Org. Chem. 2000, 65, 6739.
(9) For the building blocks for medicines, see: Korte, A.; Legros, J.; Bolm,
C. Synlett 2004, 13, 2397 and references therein.
(10) For the building blocks for organic compounds, see: Miller, R. B.; Frincke,
J. M. J. Org. Chem. 1980, 45, 5312.
(11) For the use as ligands for transition metals by deprotonation, see: (a)
Cadierno, V.; Diez, J.; Gamasa, M. P.; Gimeno, J.; Lastra, E. Coord. Chem.
ReV. 1999, 193-195, 147. (b) Zargarian, D. Coord. Chem. ReV. 2002, 233-
234, 157. (c) Leino, R.; Lehmus, P.; Lehtonen, A. Eur. J. Inorg. Chem.
2004, 3201.
(1) (a) Kakiuchi, F.; Murai, S. Top. Organomet. Chem. 1999, 3, 47. (b) Guari,
Y.; Sabo-Etienne, S.; Chaudret, B. Eur. J. Inorg. Chem. 1999, 1047. (c)
Dyker, G. Angew. Chem., Int. Ed. Engl. 1999, 38, 1698. (d) Ritleng, V.;
Sirlin, C.; Pfeffer, M. Chem. ReV. 2002, 102, 1731.
(2) (a) Chatani, N.; Ie, Y.; Kakiuchi, F.; Murai, S. J. Org. Chem. 1997, 62,
2604. (b) Jia, C.; Piao, D.; Oyamada, J.; Lu, W.; Kitamura, T.; Fujiwara,
Y. Science 2000, 287, 1992. (c) Lim, S.-G.; Ahn, J.-A.; Jun, C.-H. Org.
Lett. 2004, 6, 4687.
(3) (a) Tan, K. L.; Bergman, R. G.; Ellman, J. A. J. Am. Chem. Soc. 2001,
123, 2685. (b) Thalji, R. K.; Ahrendt, K. A.; Bergman, R. G.; Ellman, J.
A. J. Am. Chem. Soc. 2001, 123, 9692. (c) Tan, K. L.; Vasudevan, A.;
Bergman, R. G.; Ellman, J. A.; Souers, A. J. Org. Lett. 2003, 5, 2131. (d)
Thalji, R. K.; Ellman, J. A.; Bergman, R. G. J. Am. Chem. Soc. 2004, 126,
7192.
(4) Kuninobu, Y.; Kawata, A.; Takai, K. J. Am. Chem. Soc. 2005, 127, 13498.
9
202
J. AM. CHEM. SOC. 2006, 128, 202-209
10.1021/ja054216i CCC: $33.50 © 2006 American Chemical Society

Synthesis of Phthalimidine and Indene Derivatives
A R T I C L E S
Table 1. Catalytic Activities of Transition Metal Complexes
phthalimidine derivative12,13 is produced by successive intramo-
lecular cyclization. A comparison between the reactivity of an
acetylene and an isocyanate toward the aromatic aldimine shows
that the isocyanate is more reactive than the acetylene.
Results and Discussion
Reaction of Aromatic Aldimines with Internal Acetylenes.
The treatment of aromatic aldimine 1a (0.50 mmol) with
acetylene 2a (0.50 mmol) in toluene (1.0 mL) in the presence
of a possible catalyst (6.0 mol %) under reflux conditions for
24 h gave indene derivatives (eq 1).14,15
yielda [%]
entry
catalyst
3a
4a
1
2
3
RhCl(PPh3)3
0
0
0
0
0
0
b
Ru3(CO)12
c
Re2(CO)10
4
5
6
7
8
9
ReCl(CO)5
ReBr(CO)5
ReBr(CO)3(CH3CN)2
[ReBr(CO)3(thf)]2c
Re(CH3)(CO)5
ReCp*(CO)3
20
74
0
20
22
0
0
0
>99
2
0
0
10
11
ReCl3(PMe2Ph)3
MnBr(CO)5
0
0
0
0
We screened several catalysts in the reaction of aldimine 1a
with 1-phenyl-1-propyne 2a (Table 1). First, we examined a
popular rhodium(I) complex, RhCl(PPh3)3, and a ruthenium
complex, Ru3(CO)12, but the reactions did not occur and
aldimine 1a remained unchanged in both cases (Table 1, entries
1 and 2). Although the ruthenium complex has been reported
to catalyze C-H bond activation of aldimine and successive
insertion of the 1-trimethylsilyl-1-propyne,16 the process stops
at the insertion stage, and further intramolecular cyclization does
not occur. The reaction did not proceed when a dinuclear
rhenium(0) complex, Re2(CO)10, was used (Table 1, entry 3).
Among the catalysts examined, a rhenium(I) complex, ReCl-
(CO)5, was found to catalyze the desired reaction and gave two
isomeric indene derivatives, 3a and 4a, though the yields were
low (both 20% yields) (Table 1, entry 4). This result suggests
that the rhenium complex has a similar ability for C-H bond
activation as Ru3(CO)12 and that the formed alkenyl-rhenium
part has sufficient nucleophilicity to add to the aldimine moiety.
The yields and selectivity were improved by changing the ligand
of the rhenium complex from chloride to bromide (Table 1,
entry 5). For the purpose of accelerating the reaction rate by
promoting ligand dissociation, ReBr(CO)3(CH3CN)2 or [ReBr-
a The yield was detemined by H NMR with 1,1,2,2-tetrachloroethane
1
as an internal standard. b 2.0 mol %. c 3.0 mol %.
(CO)3(thf)]2 was used as the catalyst (Table 1, entries 6 and 7).
Although ReBr(CO)3(CH3CN)2 did not afford the product at
all, indene derivative 3a was obtained quantitatively by using
[ReBr(CO)3(thf)]2. Methyl-rhenium complex, Re(CH3)(CO)5,
facilitated the reaction, but the yield of 3a was very low (Table
1, entry 8). The formation reaction of indene derivatives did
not occur with rhenium(I) complex, ReCp*(CO)3, rhenium(III)
complex, ReCl3(PMe2Ph)3, or manganese(I) complex, MnBr-
(CO)5 (Table 1, entries 9-11).
The highest yield and selectivity could be obtained by using
toluene as a solvent in the reaction of aromatic aldimine 1a
with acetylene 2a (Table 2, entry 1). In octane, the reaction
proceeded quantitatively, but the selectivity of the products was
low (Table 2, entry 2). In polar solvents such as THF and
methylene chloride, the indene derivatives were obtained in low
yields (Table 2, entries 3 and 4). When more polar solvents
were used, such as 1,3-dimethyl-2-imidazolidinone (DMI) and
dimethylformamide (DMF), the yields were very low (Table 2,
entries 5 and 6).
(12) Phthalimidine (isoindolinone, benzo-γ-lactam) has a five-membered ring
with one nitrogen atom and is a part of the structure of bioactive
compounds: (a) Fajardo, V.; Elango, V.; Cassels, B. K.; Shamma, M.
Tetrahedron Lett. 1982, 23, 39. (b) Valencia, E.; Freyer, A. J.; Shamma,
M. Tetrahedron Lett. 1984, 25, 599. (c) Valencia, E.; Fajardo, V.; Freyer,
A. J.; Shamma, M. Tetrahedron Lett. 1985, 26, 993. (d) Takahashi, I.;
Kawakami, T.; Hirano, E.; Yokota, H.; Kitajima, H. Synlett 1996, 353 and
references therein. (e) Moreau, A.; Couture, A.; Deniau, E.; Grandclaudon,
P. J. Org. Chem. 2004, 69, 4527.
Although the reaction of aromatic aldimine 1a with acetylene
2a proceeded in quantitative yields at both 115 °C and 80 °C,
the selectivity of indene derivatives 3a and 4a was low at 80
°C (3a:4a ) 54:46). Even at 25 °C, the indene derivative 4a
could be obtained catalytically (21%).
Then, we varied the substituents of aldimines and alkynes
(Table 3). By the reaction of 1-phenyl-1-propyne (2a) with
aldimine 1b instead of 1a, the selectivity reversed and the indene
derivative 4b was obtained selectively (entry 2). The reaction
did not proceed with the oxime or hydrazone of an aldehyde
instead of the aldimine. Treatment of diphenylacetylene (2b)
and aldimine 1a with [ReBr(CO)3(thf)]2 afforded the indene
derivative quantitatively (entry 3). Aldimines bearing electron-
donating groups, such as methoxy and methyl groups at the
para-position of the aldimine, gave the corresponding indene
derivatives in excellent yields (entries 4 and 5). A reaction of
(13) Several synthetic methods of phthalimidine derivatives using transition metal
compounds have been reported: (a) Uozumi, Y.; Kawasaki, N.; Mori, E.;
Mori, M.; Shibasaki, M. J. Am. Chem. Soc. 1989, 111, 3725. (b) Duckworth,
D. M.; Lee-Wong, S.; Slawin, A. M. Z.; Smith, E. H.; Williams, D. J. J.
Chem. Soc., Perkin Trans. 1 1996, 815. (c) Couty, S.; Liegault, B.; Meyer,
C.; Cossy, J. Org. Lett. 2004, 6, 2511. (d) Orito, K.; Horibata, A.; Nakamura,
T.; Ushito, H.; Nagasaki, H.; Yuguchi, M.; Yamashita, S.; Tokuda, M. J.
Am. Chem. Soc. 2004, 126, 14342.
(14) The 1H NMR yields were determined by using 1,1,2,2-tetrachloroethane
as an internal standard.
(15) Heat and/or a rhenium catalyst promote interconversion of substituents at
1,2-position of the indene framework. The elucidation of the mechanism
is now under consideration.
(16) Kakiuchi, F.; Sato, T.; Tsujimoto, T.; Yamauchi, M.; Chatani, N.; Murai,
S. Chem. Lett. 1998, 1053.
9
J. AM. CHEM. SOC. VOL. 128, NO. 1, 2006 203

A R T I C L E S
Kuninobu et al.
Table 2. Investigation of the Solvent
yielda [%]
entry
solvent
3a
4a
Figure 1. X-ray crystal structure of indene derivative 3f.
1
2
3
4
5
6
toluene
Octane
THF
>99
89
0
0
11
17
29
10
0
yields decreased when substituents were attached to the ortho-
position of the aldimines. For example, the indene derivative
was obtained in 40% yield by the reaction of an aldimine bearing
ortho-methyl group with 2b (entry 8), and an aldimine with an
ortho-methoxy group did not afford the corresponding indene
derivative (entry 9). The reaction of 2b with benzaldehyde or
acetophenone did not proceed at all. The imine nitrogen atom
could coordinate more strongly to the rhenium center than the
oxygen atoms and promoted the C-H bond activation. The
reaction of 2b with an N,N-dimethylhydrazone of benzaldehyde
did not proceed at all, and the starting materials were recovered
completely. In contrast, the reaction of 2b with an N,N-
dimethylhydrazone of acetophenone produced the insertion
product of the acetylene after C-H bond activation in 21%
yield, although most of the starting materials were recovered
unchanged (both in 75% yields).
CH2Cl2
6
7
0
DMIb
DMFc
a The yield was detemined by H NMR with 1,1,2,2-tetrachloroethane
as an internal standard. b 1,3-Dimethyl-2-imidazolidinone. c Dimethylfor-
mamide.
1
Table 3. Rhenium-Catalyzed Reaction of an Aromatic Aldimine
with an Acetylene
From our experiments, it was found that acetylenes bearing
at least one aryl group gave the corresponding indene derivatives
(entries 10 and 11). Indene derivatives could not be obtained
by the reaction of aldimine with 6-dodecyne, 1-trimethylsilyl-
1-propyne, bis(trimethylsilyl)acetylene.
The detailed structure of the indene framework was deter-
mined by X-ray crystal structure analysis (Figure 1). By the
reaction of N-phenyl aldimine (R1 ) Ph) with diphenylacetylene,
indene derivative 3f could be obtained in 93% yield (Table 1,
entry 6). After isolation by silica gel column chromatography
and recrystalization from toluene/hexane, yellow single crystals
of indene derivative 3f could be obtained.
The X-ray crystal structure analysis showed that the indene
derivative 3f has an aminoindene framework (Figure 1). The
bond length of C2-C3 is shorter than that of C1-C2, C3-C4,
and C5-C1, and is suitable for that of the CdC double bond.
The bond length of C3-N1 is also appropriate for that of the
C-N single bond. The results that C2, C3, C4, and N1 are
located on almost the same plane and C1 is a sp3 carbon atom
also indicate that 3f has an aminoindene framework.
When the proposed reaction was carried out with ReBr(CO)5
under an atmosphere of carbon monoxide (1.0 atm), an indene
derivative was not obtained and the starting materials 1a and
2a were recovered quantitatively. This result and the fact that
the catalytic activity of [ReBr(CO)3(thf)]2 is higher than that of
ReBr(CO)5 indicated that the formation step of one or more
vacant coordination sites as a result of the carbonyl ligand(s)
leaving the rhenium center is important to promote the reaction.
The proposed reaction mechanism is as follows (Scheme 1):
(1) Coordination of a nitrogen atom of an imine to a rhenium
a Isolated yield. The yield determined by 1H NMR is reported in
parentheses. b The ratios of indene derivatives 3 and 4. c 1-Phenyl-1-propyne
(1.1 equiv), 135 °C. d 135 °C.
an aldimine possessing a para-phenyl group with 2b gave the
indene derivative 3b in good yield (entry 6). However, an
aldimine bearing an electron-withdrawing trifluoromethyl group
at the para-position gave the corresponding indene derivative
in low yield (entry 7). In contrast to the para substituents, the
9
204 J. AM. CHEM. SOC. VOL. 128, NO. 1, 2006

Synthesis of Phthalimidine and Indene Derivatives
A R T I C L E S
t
6a (R1 ) H; R2 ) Bu; R3 ) Ph) was obtained in 73% yield
and 1a was recovered in 23% yield. To improve the catalytic
activity of the rhenium complex, [ReBr(CO)3(thf)]2 was used,
and 6a was formed in quantitative yield (Table 4, entry 1).22,23
In this reaction, a functionalized compound at two ortho-
positions did not form.24 The rhenium complex Re(CH3)(CO)5
showed low reactivity (4% yield of 6a). The reaction did not
proceed with other potential catalysts such as Ru3(CO)12, RuH2-
(CO)(PPh3)3, and RhCl(PPh3)3.
Scheme 1. Proposed Mechanism of the Formation of Indene
Derivatives
The phthalimidine synthesis proceeded in THF (bath tem-
perature ) 115 °C), hexane (bath temperature ) 80 °C), and
toluene as a solvent, and 6a was obtained in 59%, 69%, and
90% yields, respectively; however, it did not proceed in
dichloromethane, N,N-dimethylformamide (DMF), or dimeth-
ylimidazolidinone (DMI) under reflux conditions.
A primary alkyl isocyanate, 2-phenylethylisocyanate, and a
secondary alkyl isocyanate, cyclohexylisocyanate, did not react
with aldimine 1a.25 In contrast, the reactions of arylisocyanates
possessing both electron-donating (p-OMe, 5b) and electron-
withdrawing groups (p-CF3, 5c) and aldimine 1a gave the
corresponding phthalimidine derivatives 6b and 6c in 85% and
quantitative yields, respectively (Table 4, entries 2 and 3).
However, allylisothiocyanate and phenylisothiocyanate did not
react with aldimine 1a.
By the reactions of aldimines bearing an electron-donating
group at the para-position (1c and 1d) with phenylisocyanate
5a, the corresponding phthalimidine derivatives 6d and 6e could
be obtained in good yields (Table 4, entries 4 and 5). The
reaction of aldimines having an electron-withdrawing group (1e
and 1f) and 5a gave phthalimidine derivatives 6f and 6g in
quantitative yields (Table 4, entries 6 and 7).26 The yields
decreased when forming phthalimidine derivatives bearing
substituents at the ortho-position (Table 4, entries 8 and 9).
N-Benzyl aldimine 1i gave a phthalimidine derivative 6j in
moderate yield (Table 4, entry 10). However, the reactions of
N-phenyl aldimine or N-methoxy aldimine with 5a did not occur.
center.17 (2) C-H bond activation at the ortho-position of the
imine moiety. Although electrophilic metalation of the acetylene
is another possibility, we are tempted to assume that the
rhenium-catalyzed reactions proceed via C-H bond activation
based on the following two experimental results. First, the
orientation of the two substituents on the products derived from
acetylenes is cis-form. If the reactions proceed via electrophilic
metalation, the orientation must be trans-form and thus it must
be difficult to promote further intramolecular cyclization. The
second experimental evidence is that these reactions proceed
in the presence of a base (K2CO3 or tributylamine) without
decreasing the yield. The electrophilic metalation must be
inhibited by the addition of the base because a proton is formed
during the reaction step.18,19 (3) Insertion of an acetylene to the
rhenium-carbon bond of the aryl-rhenium intermediate. (4)
Intramolecular nucleophilic attack of the formed alkenylrhenium
moiety to a carbon atom of the imine. (5) Reductive elimination
and 1,3-rearrangement of hydrogen atoms (or vice versa).
Reaction of Aromatic Aldimines with Isocyanates. Because
rhenium has a lower electronegativity than rhodium or ruthe-
nium, a carbon-rhenium bond is expected to be more polarized
than a carbon-rhodium or a carbon-ruthenium bond. Therefore,
we thought that it might be possible to promote the insertion of
polar unsaturated molecules into a C-H bond by using a
rhenium catalyst. As a result of our investigations on the
insertion of polar unsaturated molecules, the rhenium-catalyzed
insertion reactions of isocyanates 5 (0.50 mmol) into the C-H
bond of aldimines 1 (R1 ) H; R2 ) tBu, 0.50 mmol) proceeded
at 90 °C to give phthalimidine derivatives (eq 2).20
(19) Although we tried to prepare or isolate the rhenium-hydride intermediate
by the quantitative reaction of [ReBr(CO)3(thf)]2 with aldimine, we could
not observe the formation of the intermediate.
(20) The 1H NMR yields of 6 were determined based on dibromomethane as
an internal standard.
(21) Rhenium complexes Re2(CO)10, ReCp*(CO)3, and ReCl3(PMe2Ph)3 and the
manganese complex MnBr(CO)5 did not promote the formation reaction
of 6a.
(22) Under reflux conditions, 6a was obtained irregularly as time passed. That
is, yields of 6a were 3% (1 h), 18% (3 h), 95% (8 h), and >99% (24 h),
respectively. These results indicate the existence of an induction time to
form active species to catalyze the formation reaction of phthalimidine
derivatives. However, the structure of the active species is still not clear.
(23) Though phthalimidine 6a was obtained with [ReBr(CO)3(thf)]2 in 1,2-
dichloroethane in quantitative yield under reflux conditions, the yield
decreased to 27% at 70 °C, and the reaction did not proceed at all at 50
°C.
(24) In the following reports, compounds derived from double C-H bond
activation and insertion of unsaturated molecules at two ortho-positions
were obtained as side products: (a) Murai, S.; Kakiuchi, F.; Sekine, S.;
Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani, N. Nature 1993, 366, 529.
(b) Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani,
N.; Murai, S. Bull. Chem. Soc. Jpn. 1995, 68, 62. (c) Kakiuchi, F.;
Tsujimoto, T.; Sonoda, M.; Chatani, N.; Murai, S. Synlett 2001, 948. (d)
Lim, Y.-G.; Han, J.-S.; Yang, S.-S.; Chun, J. H. Tetrahedron Lett. 2001,
42, 4853. (e) Lim, Y.-G.; Lee, K.-H.; Koo, B. T.; Kang, J.-B. Tetrahedron
Lett. 2001, 42, 7609. (f) Lim, Y.-G.; Han, J.-S.; Koo, B. T.; Kang, J.-B. J.
Mol. Catal. A: 2004, 209, 41.
(25) To investigate the reason phthalimidine derivatives were not formed using
alkyl isocyanate, we carried out the reaction without aldimine. In 1,2-
dichloroethane in the presence of [ReBr(CO)3(thf)]2 under reflux conditions,
2-phenylethylisocyanate was recovered quantitatively. Though this result
shows that the problems are not in the stability of alkyl isocyanate, the
reason is not clear.
Among the catalysts examined,21 the rhenium(I) complex
ReBr(CO)5 proved to have a catalytic activity; phthalimidine
(17) There is another possible pathway: C-H bond activation is reversible and
can occur at all positions on the aromatic ring. After C-H bond activation,
the coordinating group acts to trap the ortho-C-H bond addition product
and stable chelated intermediate. See: Zhang, X.; Kanzelberger, M.; Emge,
T. J.; Goldman, A. S. J. Am. Chem. Soc. 2004, 126, 13192.
(18) There have been some reports on the synthesis of ortho-rhenated complexes.
Ortho-rhenation of aromatic imines with Re(CH2Ph)(CO)5: (a) Bo¨hm, A.;
Su¨nkel, K.; Polborn, K.; Beck, W. J. Organomet. Chem. 1998, 552, 237.
Ortho-rhenation of phenylpyridine derivatives with Re(CH2Ph)(CO)5: (b)
Djukic, J.-P.; Maisse, A.; Pfeffer, M.; Do¨tz, K. H.; Nieger, M. Organo-
metallics 1999, 18, 2786.
(26) The reactivities of aldimines bearing an electron-donating or an electron-
withdrawing group toward acetylenes or isocyanates are opposite. The
reason for these results is not clear yet.
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J. AM. CHEM. SOC. VOL. 128, NO. 1, 2006 205

A R T I C L E S
Kuninobu et al.
Table 4. Formation of Phthalimidine Derivatives by the Reaction
of Aldimines with Isocyanates
and polar molecules (eq 3). The investigations were performed
by the reaction of aldimine 1a (1.0 equiv), diphenylacetylene
2b (1.0 equiv), and phenylisocyanate 5a (1.0 equiv) in the
presence of a rhenium catalyst, [ReBr(CO)3(thf)]2.19 In both
toluene and 1,2-dichloroethane, isocyanate 5a reacted with
aldimine 1a more efficiently than diphenylacetylene 2b and gave
the corresponding phthalimidine derivative 6a in 62% and 57%
yields, respectively. This result shows that a polar unsaturated
molecule is more reactive than a nonpolar one. The tendency
with the rhenium catalyst is opposite to that reported with
ruthenium and rhodium catalysts.27,28
a Isolated yield. The yield determined by 1H NMR is reported in
parentheses.
Scheme 2. Proposed Mechanism for the Formation of
Phthalimidine Derivatives
Conclusion
We have succeeded in the quantitative synthesis of indene
and phthalimidine derivatives via C-H bond activation by the
reactions of aromatic aldimines with phenyl acetylenes and
aromatic isocyanates catalyzed by a rhenium complex, [ReBr-
(CO)3(thf)]2. There are only a few precedents for the rhenium-
catalyzed C(sp2)-H bond activation.5,6 In addition, to our
knowledge, the intramolecular nucleophilic addition of orga-
nometallic species derived from C-H bond activation to an
imine moiety has not been reported. These reactions need only
a catalytic amount of the metal reagent and a few reaction steps
compared with the reported synthetic methods of indene and
phthalimidine derivatives. Therefore, it will become a useful
method to synthesize indene and phthalimidine derivatives.
Since examples of the insertion of a polarized unsaturated
molecule via C-H bond activation are still rare, the results
obtained in this paper will help the development of synthetic
strategies via C-H bond activation. We are currently working
to develop new rhenium-catalyzed synthetic methods via C-H
bond activation.
The proposed mechanism for the formation of phthalimidine
derivatives is shown in Scheme 2. Owing to the coordination
of a nitrogen atom of aldimine 1 to a rhenium center, the
rhenium atom approaches close to the aromatic C-H bond at
the ortho-position of the imine moiety.4,17 After C-H bond
activation, isocyanate 5 inserts into the aromatic carbon-
rhenium bond. This step is unique because it has been difficult
for the previous transition metal-catalyzed transformations via
C-H bond activation to promote the insertion of polar unsatur-
ated molecules. Intramolecular nucleophilic addition of the
amido-rhenium moiety to an imine group of an intermediate
A gives a phthalimidine framework. Though rhenium-catalyzed
intramolecular nucleophilic cyclizations via C-H bond activa-
tion have been reported,4 nucleophilic attack of the rhenium-
nitrogen moiety to CdN bond is new. After the reductive
elimination occurs, the active rhenium(I) species is regenerated
and the phthalimidine derivative 6 can be obtained.
Experimental Section
General. All reactions were carried out in a dry solvent under an
argon atmosphere. 1,2-Dichloroethane and toluene were purchased from
Wako Pure Chemical Industries and were dried, distilled, and degassed
before use. [ReBr(CO)3(thf)]2 was prepared by heating a THF solution
of ReBr(CO)5 at reflux temperature for 16 h as reported.29 The resulting
solution was concentrated in vacuo and was recrystallized from THF/
(27) Kakiuchi, F.; Sekine, S.; Tanaka, Y.; Kamatani, A.; Sonoda, M.; Chatani,
N.; Murai, S. Bull. Chem. Soc. Jpn. 1995, 68, 62.
(28) (a) Chatani, N.; Fukuyama, T.; Kakiuchi, F.; Murai, S. J. Am. Chem. Soc.
1996, 118, 493. (b) Tan, K. L.; Bergman, R. G.; Ellman, J. A. J. Am. Chem.
Soc. 2002, 124, 13964. (c) Lim, S.-G.; Ahn, J.-A.; Jun, C.-H. Org. Lett.
2004, 6, 4687.
Comparison of the Reactivity between an Acetylene and
an Isocyanate. We compared the reactivity between nonpolar
(29) Du, S.; Kautz, J. A.; McGrath, T. D.; Stone, F. G. A. Organometallics
2003, 22, 2842.
9
206 J. AM. CHEM. SOC. VOL. 128, NO. 1, 2006

Synthesis of Phthalimidine and Indene Derivatives
A R T I C L E S
hexane to give [ReBr(CO)3(thf)]2 as a white solid in 75% yield.30
Aldimines were prepared by condensation of the corresponding
aldehydes with the corresponding amines in the presence of molecular
sieves (4 Å) in hexane at 50 °C for 10 h and were used after distillation.
The structures of 1a,31 1b,32 1c,33 1d,33 1g,34 1h,35 and 1i36 were
determined by the comparison with the data, which were already
reported. The spectral data of 1e and 1f are reported in the Supporting
Information. Acetylenes and isocyanates were purchased from Wako
Pure Chemical Industries, Tokyo Kasei Kogyo Co., and Aldrich Co.
and used after distillation.
(w). Anal.Calcd for C22H19N: C, 88.85; H, 6.44; N, 4.71. Found: C,
88.65; H, 6.65; N, 4.65.
N-tert-Butyl-2,3-diphenyl-3H-inden-1-amine (3c). H NMR (400
1
MHz, CDCl3) δ 1.12 (s, 9H), 4.87 (s, 1H), 7.04 (d, J ) 7.6 Hz, 2H),
7.09-7.17 (m, 6H), 7.22 (t, J ) 7.7 Hz, 2H), 7.28-7.31 (m, 1H), 7.34
(d, J ) 8.4 Hz, 2H), 7.48 (d, J ) 6.9 Hz, 1H); 13C NMR (100 MHz,
CDCl3) δ 31.03 (3C), 54.88 (1C), 56.66 (1C), 119.90 (2C), 123.77
(1C), 125.41 (1C), 126.35 (1C), 126.45 (2C), 128.12 (1C), 128.17 (2C),
128.34 (1C), 128.46 (2C), 128.86 (1C), 136.68 (1C), 137.03 (1C),
140.41 (1C), 143.21 (1C), 144.33 (1C), 147.39 (1C); IR (Nujol, ν/cm-1
)
1H (400 MHz) and 13C (100 MHz) NMR spectra were recorded using
a JEOL JNM-LA400 spectrometer. Proton chemical shifts are reported
relative to Me4Si (CDCl3) at δ 0.00 ppm or residual solvent peak (CDCl3
at δ 7.26 ppm). Carbon chemical shifts are reported relative to CDCl3
at δ 77.00 ppm. IR spectra were recorded on Nicolet Prote´ge´ 460. The
crystal was mounted on a Rigaku RAXIS-IV Imaging Plate diffracto-
meter for data collection using MoKR (graphite monochromated, λ )
0.7107 Å) radiation.
General Procedure for the Reaction of Aldimines with Acety-
lenes. The mixture of aldimine (0.500 mmol), acetylene (0.500 mmol),
and [ReBr(CO)3(thf)]2 (12.7 mg, 0.0150 mmol) in toluene (1.0 mL)
was refluxed for 24 h. After the solvent was removed in vacuo, the
products were isolated by silica gel column chromatography.
N-tert-Butyl-3-methyl-2-phenyl-3H-inden-1-amine (3a). 1H NMR
(400 MHz, CDCl3) δ 1.05 (s, 9H), 1.18 (d, J ) 7.5 Hz, 3H), 3.28 (brs,
1H), 3.86 (q, J ) 7.5 Hz, 1H), 7.21-7.28 (m, 2H), 7.31 (t, J ) 7.2
Hz, 1H), 7.38-7.46 (m, 6H); 13C NMR (100 MHz, CDCl3) δ 16.68
(1C), 30.74 (3C), 44.02 (1C), 54.66 (1C), 119.74 (1C), 122.45 (1C),
124.72 (1C), 126.10 (1C), 126.25 (1C), 128.20 (2C), 128.86 (2C),
137.06 (1C), 138.95 (1C), 140.86 (1C), 144.33 (1C), 147.55 (1C); IR
(Nujol, ν/ cm-1) 3056 (w), 3021 (w), 2962 (m), 1602 (m), 1494 (m),
1389 (m), 1221 (m), 1200 (w), 1153 (w), 1135 (w), 1074 (m), 1019
(w), 933 (w), 912 (w), 869 (w), 843 (w), 768 (w), 757 (s), 738 (w),
698 (s). Anal.Calcd for C20H23N: C, 86.59; H, 8.36; N, 5.05. Found:
C, 86.70; H, 8.38; N, 4.92.
N-tert-Butyl-2-methyl-3-phenyl-3H-inden-1-amine (4a). 1H NMR
(400 MHz, CDCl3) δ 1.02 (s, 9H), 2.03 (s, 3H), 4.69 (s, 1H), 7.19-
7.33 (m, 6H), 7.39 (t, J ) 7.3 Hz, 2H), 7.55 (d, J ) 7.2 Hz, 1H); 13C
NMR (100 MHz, CDCl3) δ 11.19 (1C), 30.81 (3C), 50.66 (1C), 62.78
(1C), 119.01 (1C), 123.41 (1C), 125.45 (1C), 126.88 (1C), 127.21 (1C),
127.92 (2C), 129.74 (2C), 134.21 (1C), 136.35 (1C), 144.90 (1C),
145.61 (1C), 147.91 (1C); IR (Nujol, ν/cm-1) 3057 (w), 3024 (w), 2961
(m), 1905 (w), 1601 (m), 1493 (w), 1441 (w), 1387 (m), 1290 (w),
1227 (w), 1153 (w), 1097 (w), 1020 (w), 792 (w), 757 (s), 735 (m),
700 (s), 665 (w). Anal.Calcd for C20H23N: C, 86.59; H, 8.36; N, 5.05.
Found: C, 86.59; H, 8.35; N, 5.00.
3061 (w), 3022 (w), 1951 (w), 1653 (w), 1601 (m), 1493 (m), 1430
(m), 1389 (w), 1378 (w), 1284 (w), 1218 (w), 1199 (m), 1121 (w),
1095 (w), 1071 (m), 1026 (m), 938 (w), 918 (w), 815 (w), 783 (m),
759 (s), 736 (m), 696 (s), 675 (w), 666 (m), 651 (m), 621 (m).
Anal.Calcd for C25H25N: C, 88.45; H, 7.42; N, 4.13. Found: C, 88.57;
H, 7.41; N, 4.03.
N-tert-Butyl-5-methoxy-2,3-diphenyl-3H-inden-1-amine (3d). 1H
NMR (400 MHz, CDCl3) δ 1.34 (s, 9H), 3.75 (s, 3H), 4.84 (s, 1H),
6.72 (d, J ) 2.1 Hz, 1H), 6.85 (d, J ) 8.3 Hz, 1H), 7.05 (d, J ) 7.5
Hz, 2H), 7.09-7.19 (m, 4H), 7.21-7.26 (m, 2H), 7.31 (d, J ) 7.8 Hz,
2H), 7.39 (d, J ) 8.4 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ 30.99
(3C), 55.33 (1C), 56.39 (1C), 58.80 (1C), 110.10 (1C), 111.94 (2C),
120.54 (2C), 126.05 (1C), 126.39 (1C), 128.08 (1C), 128.12 (1C),
128.45 (2C), 128.68 (2C), 134.55 (1C), 137.10 (1C), 137.13 (1C),
140.55 (1C), 142.90 (1C), 149.21 (1C), 158.28 (1C); IR (Nujol, ν/cm-1
)
3322 (w), 3087 (w), 3042 (w), 3024 (w), 1653 (w), 1600 (s), 1494
(m), 1433 (w), 1388 (w), 1367 (w), 1280 (s), 1255 (w), 1218 (m), 1181
(w), 1136 (m), 1102 (m), 1071 (m), 1027 (m), 876 (m), 850 (m), 809
(m), 795 (w), 756 (s), 740 (s), 729 (w), 696 (s), 681 (w), 650 (w), 616
(w). Anal.Calcd for C26H27NO: C, 84.51; H, 7.37; N, 3.79. Found: C,
84.74; H, 7.51; N, 3.76.
N-tert-Butyl-5-methyl-2,3-diphenyl-3H-inden-1-amine (3e). 1H
NMR (400 MHz, CDCl3) δ 1.13 (s, 9H), 2.27 (s, 3H), 3.40 (br, 1H),
4.84 (s, 1H), 6.96 (s, 1H), 7.04-7.10 (m, 5H), 7.12-7.16 (m, 2H),
7.20 (t, J ) 8.1 Hz, 2H), 7.33-7.38 (m, 3H); 13C NMR (100 MHz,
CDCl3) δ 21.32 (1C), 30.95 (3C), 54.77 (1C), 56.33 (1C), 119.59 (1C),
124.59 (1C), 126.12 (1C), 126.32 (2C), 127.14 (1C), 128.03 (2C),
128.12 (2C), 128.39 (1C), 128.72 (2C), 135.10 (1C), 135.57 (1C),
137.06 (1C), 140.59 (1C), 141.61 (1C), 143.13 (1C), 147.59 (1C); IR
(Nujol, ν/cm-1) 3308 (w), 3081 (w), 3055 (w), 3023 (w), 2950 (w),
1937 (w), 1885 (w), 1599 (s), 1494 (m), 1439 (m), 1388 (w), 1323
(w), 1225 (m), 1200 (m), 1130 (m), 1097 (w), 1069 (m), 1049 (w),
1026 (w), 939 (w), 912 (w), 885 (w), 857 (m), 822 (m), 809 (m), 797
(m), 751 (m), 731 (m), 694 (s), 647 (m), 633 (m), 615 (m). Anal. Calcd.
for C26H27N: C, 88.34; H, 7.70; N, 3.96. Found: C, 88.13; H, 7.69;
N, 3.85.
2-Methyl-N,3-diphenyl-3H-inden-1-amine (4b). 1H NMR (400
MHz, CDCl3) δ 2.27 (d, J ) 1.8 Hz, 3H), 5.47 (s, 1H), 6.61 (d, J )
8.1 Hz, 2H), 6.67 (t, J ) 7.6 Hz, 1H), 7.11-7.19 (m, 3H), 7.25-7.28
(m, 1H), 7.35-7.41 (m, 6H), 7.48 (d, J ) 7.2 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 11.90 (1C), 62.04 (1C), 113.67 (1C), 117.50 (1C),
119.34 (1C), 122.90 (1C), 125.85 (2C), 126.90 (2C), 127.90 (1C),
128.25 (1C), 129.05 (2C), 129.14 (2C), 135.13 (1C), 135.57 (1C),
N-tert-Butyl-2,3,5-triphenyl-3H-inden-1-amine (3f). 1H NMR (400
MHz, CDCl3) δ 1.14 (s, 9H), 3.46 (br, 1H), 4.92 (s, 1H), 7.06-7.16
(m, 6H), 7.20-7.26 (m, 3H), 7.32-7.39 (m, 5H), 7.52 (d, J ) 9.6 Hz,
4H); 13C NMR (100 MHz, CDCl3) δ 31.04 (3C), 54.90 (1C), 56.71
(1C), 120.23 (1C), 122.65 (1C), 125.57 (1C), 126.41 (1C), 126.50 (1C),
126.86 (1C), 127.06 (2C), 127.34 (1C), 128.15 (2C), 128.25 (2C),
128.52 (2C), 128.59 (2C), 128.83 (2C), 136.97 (1C), 138.50 (1C),
140.24 (1C), 141.37 (1C), 143.06 (1C), 143.64 (1C), 148.08 (1C); IR
(Nujol, ν/ cm-1) 3022 (w), 1951 (w), 1653 (m), 1601 (m), 1439 (m),
1430 (m), 1389 (w), 1378 (w), 1284 (w), 1218 (w), 1199 (m), 1121
(w), 1095 (w), 1071 (m), 1026 (m), 938 (w), 918 (w), 815 (w), 783
(m), 759 (s), 736 (m), 696 (s), 675 (w), 666 (w), 651 (m), 621 (m).
Anal.Calcd for C31H29N: C, 89.60; H, 7.03; N, 3.37. Found: C, 89.45;
H, 7.07; N, 3.30.
N-tert-Butyl-5-(trifluoromethyl)-2,3-diphenyl-3H-inden-1-
amine (3g). 1H NMR (400 MHz, CDCl3) δ 1.12 (s, 9H), 3.44 (br, 1H),
4.92 (s, 1H), 7.03 (d, J ) 6.9 Hz, 2H), 7.14-7.19 (m, 4H), 7.26 (t, J
) 7.3 Hz, 2H), 7.31 (d, J ) 7.5 Hz, 2H), 7.37 (s, 1H), 7.58 (s, 2H);
13C NMR (100 MHz, CDCl3) δ 30.88 (3C), 55.22 (1C), 56.64 (1C),
120.12 (1C), 120.56 (1C), 120.59 (1C), 123.94 (1C), 123.97 (1C),
142.22 (1C), 144.73 (1C), 145.11 (1C), 147.71 (1C); IR (Nujol, ν/cm-1
)
3095 (m), 3049 (w), 1907 (w), 1599 (m), 1502 (w), 1430 (w), 1378
(m), 1340 (w), 1315 (m), 1244 (s), 1174 (w), 1153 (s), 1131 (m), 1092
(w), 1075 (w), 1039 (m), 1020 (m), 991 (m), 972 (w), 960 (w), 937
(m), 908 (s), 876 (m), 850 (m), 773 (s), 744 (w), 692 (s), 623 (m), 584
(30) Vitali, D.; Calderazzo, F. Gazz. Chim. Ital. 1972, 102, 587.
(31) Nongkunsarn, P.; Ramsden, C. A. Tetrahedron 1997, 53, 3805.
(32) Mayer, M. F.; Hossain, M. M. J. Org. Chem. 1998, 63, 6839.
(33) Cordes, E. H.; Jencks, W. P. J. Am. Chem. Soc. 1963, 85, 2843.
(34) Forth, M. A.; Mitchell, M. B.; Smith, S. A. C.; Gombatz, K.; Snyder, L. J.
Org. Chem. 1994, 59, 2616.
(35) Girling, I. R.; Widdowson, D. A. J. Chem. Soc., Perkin Trans. 1 1988,
1317.
(36) Ishihara, K.; Miyata, M.; Hattori, K.; Tada, T.; Yamamoto, H. J. Am. Chem.
Soc. 1994, 116, 10520.
9
J. AM. CHEM. SOC. VOL. 128, NO. 1, 2006 207

A R T I C L E S
Kuninobu et al.
126.90 (1C), 126.94 (1C), 127.12 (1C), 127.45 (1C), 128.14 (2C),
128.30 (2C), 128.70 (2C), 128.74 (2C), 136.13 (1C), 138.84 (1C),
147.51 (1C), 147.86 (1C); IR (Nujol, ν/cm-1) 3316 (w), 1616 (m), 1601
(w), 1493 (w), 1392 (w), 1377 (m), 1328 (s), 1275 (m), 1235 (w), 1160
(s), 1120 (w), 1109 (w), 1071 (w), 1060 (m), 929 (m), 913 (m), 850
(w), 816 (m), 753 (m), 698 (w), 691 (w), 681 (m), 637 (w). Anal.Calcd
for C26H24F3N: C, 76.64; H, 5.94; N, 3.44. Found: C, 76.54; H, 6.00;
N, 3.31.
1H, NH), 3.83 (s, 3H, MeO), 5.73 (s, 1H, CH-NH), 6.96 (d, 2H, Ar,
J ) 8.7 Hz), 7.28 (d, 2H, J ) 8.7 Hz), 7.49 (t, 1H, J ) 6.8 Hz), 7.55-
7.60 (m, 2H, Ar), 7.86 (d, 1H, Ar, J ) 7.5 Hz); 13C NMR (100 MHz,
CDCl3) δ 30.88 (3C), 50.33 (1C), 55.33 (1C), 73.29 (1C), 114.03 (2C),
123.03 (1C), 123.54 (1C), 128.88 (1C), 129.37 (2C), 129.52 (1C),
131.94 (1C), 132.10 (1C), 145.91 (1C), 158.46 (1C), 166.75 (1C); IR
(Nujol, ν/cm-1) 3367 (w), 2042 (m), 1980 (m), 1965 (m), 1699 (m),
1607 (w), 1514 (m), 1298 (w), 1249 (m), 1123 (w), 1103 (w), 1026
(w); EI-MS (+) m/z ) 310 (M+). Anal.Calcd for C19H22N2O2: C, 73.52;
H, 7.14; N, 9.03. Found: C, 73.33; H, 7.05; N, 9.04.
N-tert-Butyl-7-methyl-2,3-diphenyl-3H-inden-1-amine (3h). 1H
NMR (400 MHz, CDCl3) δ 0.75 (s, 9H), 2.66 (s, 3H), 5.14 (s, 1H),
6.99 (t, J ) 6.9 Hz, 2H), 7.14-7.25 (m, 6H), 7.27-7.38 (m, 5H); 13
C
3-tert-Butylimino-2-(4-trifluoromethyl-phenyl)-2,3-dihydro-isoin-
dol-1-one (6c). 1H NMR (400 MHz, CDCl3) δ 0.94 (s, 9H, tBu), 1.83
(s, 1H, NH), 5.98 (s, 1H, CH-NH), 7.50-7.54 (m, 1H, Ar), 7.59-
7.63 (m, 4H, Ar), 7.70 (d, 2H, Ar, J ) 8.4 Hz), 7.87 (d, 2H, Ar, J )
7.5 Hz); 13C NMR (100 MHz, CDCl3) δ 31.03 (3C), 50.55 (1C), 73.16
(1C), 117.92 (1C), 123.50 (2C), 125.28 (1C), 125.65 (1C), 126.48 (2C),
127.85 (1C), 129.05 (1C), 131.32 (1C), 132.37 (1C), 140.26 (1C),
145.33 (1C), 166.44 (1C); IR (Nujol, ν/cm-1) 2042 (m), 1981 (m),
1966 (m), 1683 (m), 1653 (w), 1612 (w), 1330 (w), 1165 (w), 1137
(w), 1121 (w), 1070 (w); EI-MS (+) m/z ) 348 (M+). Anal.Calcd for
C19H19F3N2O: C, 65.51; H, 5.50; N, 8.04. Found: C, 65.24; H, 5.52;
N, 8.00.
NMR (100 MHz, CDCl3) δ 18.76 (1C), 31.23 (3C), 52.71 (1C), 64.33
(1C), 118.17 (1C), 126.45 (1C), 127.19 (1C), 127.45 (1C), 127.75 (1C),
128.03 (2C), 128.52 (2C), 129.17 (2C), 129.66 (2C), 134.90 (1C),
135.70 (1C), 135.93 (1C), 138.77 (1C), 143.61 (1C), 143.90 (1C),
146.35 (1C); IR (Nujol, ν/cm-1) 3050 (w), 3029 (w), 2960 (w), 1954
(w), 1888 (w), 1597 (m), 1499 (w), 1443 (m), 1385 (w), 1377 (w),
1226 (w), 1213 (w), 1156 (w), 1104 (w), 1089 (w), 1074 (m), 1049
(w), 1029 (m), 959 (w), 917 (m), 847 (w), 797 (w), 776 (m), 755 (s),
725 (w), 700 (s), 632 (m), 603 (w). Anal.Calcd for C26H27N: C, 88.34;
H, 7.70; N, 3.96. Found: C, 88.29; H, 7.71; N, 3.91.
N-tert-Butyl-3-hexyl-2-phenyl-3H-inden-1-amine (3j). 1H NMR
(400 MHz, CDCl3) δ 0.75 (t, J ) 7.1 Hz, 3H), 1.04 (s, 9H), 0.87-
1.12 (m, 8H), 1.55-1.62 (m, 1H), 1.81-1.89 (m, 1H), 3.94 (t, J ) 4.9
Hz, 1H), 7.19-7.32 (m, 3H), 7.38-7.47 (m, 6H); 13C NMR (100 MHz,
CDCl3) δ 14.07 (1C), 22.43 (1C), 23.76 (1C), 29.39 (1C), 30.32 (1C),
30.88 (3C), 31.46 (1C), 49.02 (1C), 54.68 (1C), 119.90 (1C), 122.61
(1C), 124.57 (1C), 126.03 (1C), 126.32 (1C), 128.37 (2C), 128.86 (2C),
137.32 (1C), 137.48 (1C), 141.72 (1C), 145.13 (1C), 146.10 (1C); IR
(Nujol, ν/ cm-1) 3059 (w), 3020 (w), 2956 (w), 1602 (m), 1493 (w),
1389 (m), 1222 (m), 1201 (w), 1072 (w), 1024 (w), 935 (w), 912 (w),
783 (w), 758 (s), 698 (s), 666 (w). HR-MS Calcd for C25H33N:
347.2613; Found: 347.2613.
3-tert-Butylimino-2-phenyl-6-methoxy-2,3-dihydro-isoindol-1-
1
t
one (6d). H NMR (400 MHz, CDCl3) δ 0.92 (s, 9H, Bu), 1.68 (s,
1H, NH), 3.89 (s, 3H, OMe), 5.83 (s, 1H, CH-NH), 7.14 (d, 1H, Ar,
J ) 8.4 Hz), 7.28-7.32 (m, 1H, Ar), 7.37 (m, 1H, Ar), 7.39-7.49 (m,
5H, Ar); 13C NMR (100 MHz, CDCl3) δ 31.08 (3C), 50.44 (1C), 55.75
(1C), 73.02 (1C), 106.29 (1C), 120.23 (1C), 124.26 (1C), 126.74 (1C),
127.41 (2C), 128.83 (2C), 133.57 (1C), 136.97 (1C), 137.75 (1C),
160.64 (1C), 166.49 (1C); IR (Nujol, ν/cm-1) 3351 (w), 2015 (w), 1916
(w), 1861 (w), 1675 (s), 1595 (w), 1497 (m), 1291 (m), 1246 (m),
1100 (w), 1040 (w); EI-MS (+) m/z ) 310 (M+). HR-MS Calcd for
C19H22N2O2: 310.1681; Found: 310.1682.
N-tert-Butyl-2-(trimethylsilyl)-3-phenyl-3H-inden-1-amine (4k).
1H NMR (400 MHz, CDCl3) δ -0.34 (s, 9H), 1.01 (s, 9H), 3.91 (s,
1H), 7.16 (t, J ) 5.2 Hz, 1H), 7.20-7.29 (m, 2H), 7.37 (d, 4.4 Hz,
4H), 7.41 (d, J ) 7.2 Hz, 1H), 7.57 (d, J ) 7.6 Hz, 1H); 13C NMR
(100 MHz, CDCl3) δ -2.48 (3C), 30.92 (3C), 45.71 (1C), 54.68 (1C),
120.56 (1C), 122.88 (1C), 123.45 (1C), 124.45 (1C), 126.52 (1C),
128.39 (2C), 129.14 (2C), 136.17 (1C), 138.73 (1C), 140.10 (1C),
143.42 (1C), 144.02 (1C); IR (Nujol, ν/cm-1) 3025 (w), 1975 (w), 1955
(w), 1935 (w), 1903 (w), 1599 (m), 1580 (w), 1558 (m), 1491 (w),
1377 (w), 1307 (w), 1249 (m), 1222 (w), 1202 (w), 1155 (w), 1140
(w), 1125 (m), 1099 (m), 1072 (m), 1047 (m), 1024 (s), 968 (w), 941
(m), 916 (w), 892 (m), 839 (s), 781 (s), 761 (m), 740 (w), 705 (s), 632
(m), 615 (m), 599 (m). HR-MS Calcd for C22H29NSi: 335.2069;
Found: 335.2068.
3-tert-Butylimino-2-phenyl-6-methyl-2,3-dihydro-isoindol-1-
one (6e). 1H NMR (400 MHz, CDCl3) δ 0.91 (s, 9H, tBu), 1.68 (s, 1H,
NH), 2.44 (s, 3H, Me), 5.82 (s, 1H, CH-NH), 7.28-7.29 (m, 1H, Ar),
7.41-7.47 (m, 6H, Ar), 7.67 (s, 1H, Ar); 13C NMR (100 MHz, CDCl3)
δ 21.28 (1C), 30.99 (3C), 50.48 (1C), 73.02 (1C), 123.06 (1C), 123.85
(2C), 126.59 (1C), 127.34 (1C), 128.74 (2C), 132.15 (1C), 132.92 (1C),
136.95 (1C), 139.10 (1C), 142.82 (1C), 166.64 (1C); IR (Nujol, ν/cm-1
)
3373 (w), 2040 (m), 1980 (m), 1965 (m), 1673 (m), 1594 (w), 1495
(w), 1108 (w); EI-MS (+) m/z ) 294 (M+). HR-MS Calcd for
C19H22N2O: 294.1732; Found: 294.1730.
3-tert-Butylimino-2,6-diphenyl-2,3-dihydro-isoindol-1-one (6f). 1H
t
NMR (400 MHz, CDCl3) δ 0.95 (s, 9H, Bu), 1.72 (s, 1H, NH), 5.90
(s, 1H, CH-NH), 7.31 (t, 1H, Ar, J ) 6.8 Hz), 7.37-7.49 (m, 7H,
Ar), 7.64-7.66 (m, 3H, Ar), 7.82 (d, 1H, Ar, J ) 7.8 Hz), 8.11 (s, 1H,
Ar); 13C NMR (100 MHz, CDCl3) δ 31.03 (3C), 50.46 (1C), 73.09
(1C), 121.99 (1C), 123.66 (1C), 126.79 (1C), 127.14 (2C), 127.50 (2C),
127.77 (1C), 128.79 (2C), 128.88 (2C), 130.92 (1C), 132.77 (1C),
136.86 (1C), 139.90 (1C), 142.28 (1C), 144.55 (1C), 166.40 (1C); IR
(Nujol, ν/ cm-1): 3357 (w), 1682 (s), 1597 (w), 1116 (w), 765 (m),
693 (m); EI-MS (+) m/z ) 356 (M+). Anal.Calcd for C24H24N2O: C,
80.87; H, 6.79; N, 7.86. Found: C, 80.62; H, 6.85; N, 7.93.
General Procedure for the Reaction of Aldimines with Isocyan-
ates. A mixture of aldimine (0.500 mmol), isocyanate (0.500 mmol),
and [ReBr(CO)3(thf)]2 (12.7 mg, 0.0150 mmol) in 1,2-dichloroethane
(1.0 mL) was refluxed for 24 h. After the solvent was removed in vacuo,
the products were isolated by silica gel column chromatography.
3-tert-Butylimino-2-phenyl-2,3-dihydro-isoindol-1-one (6a). 1H
t
NMR (400 MHz, CDCl3) δ 0.93 (s, 9H, Bu), 1.72 (s, 1H, NH), 5.88
(s, 1H, CH-NH), 7.28-7.31 (m, 1H, Ar), 7.39-7.46 (m, 4H, Ar),
7.48-7.52 (m, 1H, Ar), 7.57-7.60 (m, 2H, Ar), 7.87 (d, 1H, Ar, J )
7.5 Hz); 13C NMR (100 MHz, CDCl3) δ 31.95 (3C), 50.44 (1C), 73.18
(1C), 123.25 (1C), 123.56 (1C), 126.74 (1C), 127.46 (2C), 128.75 (2C),
128.94 (1C), 131.95 (1C), 132.01 (1C), 136.79 (1C), 145.66 (1C),
166.49 (1C); IR (Nujol, ν/cm-1) 3367 (w), 1675 (m), 1595 (m), 1501
(m), 1489 (m), 1244 (w), 1218 (w), 1108 (m), 1035 (w), 1019 (w),
754 (m), 692 (m), 664 (w), 636 (w); EI-MS (+) m/z ) 280 (M+).
Anal.Calcd for C18H20N2O: C, 77.11; H, 7.19; N, 9.99. Found: C,
77.03; H, 7.11; N, 9.96.
3-tert-Butylimino-2-phenyl-6-trifluoromethyl-2,3-dihydro-isoin-
dol-1-one (6g). 1H NMR (400 MHz, CDCl3) δ 0.94 (s, 9H, tBu), 1.74
(s, 1H, NH), 5.94 (s, 1H, CH-NH), 7.34 (t, 1H, Ar, J ) 7.2 Hz), 7.40
(d, 2H, Ar, J ) 7.2 Hz), 7.47 (t, 2H, Ar, J ) 7.8 Hz), 7.74 (d, 1H, Ar,
J ) 7.8 Hz), 7.86 (d, 1H, Ar, J ) 7.8 Hz), 8.15 (s, 1H, Ar); 13C NMR
(100 MHz, CDCl3) δ 30.97 (3C), 50.66 (1C), 73.15 (1C), 120.94 (1C),
122.32 (1C), 124.14 (1C), 125.03 (1C), 127.14 (1C), 127.34 (2C),
128.94 (2C), 131.66 (1C), 132.81 (1C), 136.33 (1C), 149.11 (1C),
165.02 (1C); IR (Nujol, ν/cm-1) 3384 (w), 2041 (m), 1979 (m), 1965
(m), 1683 (m), 1595 (m), 1325 (m), 1242 (m), 1167 (m), 1127 (m),
1052 (w), 1037 (w), 1020 (w), 859 (m), 778 (m), 747 (m); EI-MS (+)
3-tert-Butylimino-2-(4-methoxy-phenyl)-2,3-dihydro-isoindol-1-
1
t
one (6b). H NMR (400 MHz, CDCl3) δ 0.96 (s, 9H, Bu), 1.63 (s,
9
208 J. AM. CHEM. SOC. VOL. 128, NO. 1, 2006

Synthesis of Phthalimidine and Indene Derivatives
A R T I C L E S
m/z ) 348 (M+). Anal.Calcd for C19H19F3N2O: C, 65.51; H, 5.50; N,
8.04. Found: C, 65.22; H, 5.43; N, 8.04.
NH), 7.00 (d, 2H, Ar, J ) 7.0 Hz), 7.13-7.27 (m, 4H, Ar), 7.45 (t,
2H, Ar, J ) 7.5 Hz), 7.54 (t, 3H, Ar, J ) 7.5 Hz), 7.61 (t, 1H, Ar, J
) 7.5 Hz), 7.68 (d, 1H, Ar, J ) 7.5 Hz), 7.90 (d, 1H, Ar, J ) 7.5 Hz);
13C NMR (100 MHz, CDCl3) δ 44.70 (1C), 73.92 (1C), 123.41 (2C),
123.65 (1C), 125.66 (1C), 126.95 (1C), 127.83 (2C), 128.17 (2C),
128.70 (1C), 129.34 (2C), 129.46 (1C), 132.35 (1C), 132.75 (1C),
3-tert-Butylimino-2-phenyl-4-methyl-2,3-dihydro-1-isoindol-1-
1
t
one (6h). H NMR (400 MHz, CDCl3) δ 0.77 (s, 9H, Bu), 1.84 (s,
1H, NH), 2.59 (s, 1H, Me), 6.23 (s, 1H, CH-NH), 7.22 (t, 1H, Ar, J
) 7.5 Hz), 7.35 (d, 1H, Ar, J ) 7.2 Hz), 7.41 (d, 1H, Ar, J ) 7.5 Hz),
7.46 (t, 2H, Ar, J ) 7.8 Hz), 7.58 (d, 2H, Ar, J ) 7.8 Hz); 7.74 (d,
1H, Ar, J ) 7.5 Hz); 13C NMR(100 MHz, CDCl3) δ 17.96 (1C), 31.01
(3C), 51.35 (1C), 72.55 (1C), 121.08 (1C), 123.43 (1C), 124.88 (1C)
128.94 (2C), 129.08 (2C), 132.08 (1C), 133.81 (1C), 134.73 (1C),
137.43 (1C), 141.84 (1C), 166.51 (1C); IR (Nujol, ν/cm-1) 3395 (w),
1675 (s), 1597 (s), 1558 (w), 1231 (w), 1119 (m), 1049 (m), 761 (m).
HR-MS Calcd for C19H22N2O: 294.1732; Found: 294.1732.
136.35 (1C), 139.15 (1C), 142.01 (1C), 166.58 (1C); IR (Nujol, ν/cm-1
)
3347 (w), 2018 (s), 1901 (s), 1680 (s), 1597 (s), 1112 (m). HR-MS
Calcd for C21H18N2O: 314.1420; Found: 314.1417.
Acknowledgment. Financial support by a Grant-in-Aid for
Scientific Research on Priority Areas (No. 14078219, “Reaction
Control of Dynamic Complexes”) from the Ministry of Educa-
tion, Culture, Sports, Science, and Technology of Japan. We
are indebted to Professor Masaichi Saito, Department of
Chemistry, Faculty of Science, Saitama University, for acquiring
HR-MS spectra. We thank Dr. Toshiyuki Oshiki, Division of
Chemistry and Biochemistry, Graduate School of Natural
Science and Technology, Okayama University, for the X-ray
crystal structure of 3f.
3-tert-Butylimino-2-phenyl-4-methoxy-2,3-dihydro-1-isoindol-1-
one (6i). 1H NMR (400 MHz, CDCl3) δ 0.95 (s, 9H, tBu), 1.94 (s, 1H,
NH), 3.96 (s, 3H, OMe), 6.11 (s, 1H, CH-NH), 7.07 (dd, 1H, Ar, J )
6.6, 2.1 Hz), 7.26 (t, 1H, Ar, J ) 6.5 Hz), 7.43-7.52 (m, 6H, Ar); 13
C
NMR (100 MHz, CDCl3) δ 30.72 (3C), 51.33 (1C), 55.22 (1C), 71.76
(1C), 113.78 (1C), 115.88 (1C), 125.65 (2C), 125.94 (1C), 128.94 (2C),
130.91 (1C), 131.28 (1C), 134.19 (1C), 137.12 (1C), 155.09 (1C),
166.29 (1C); IR (Nujol, ν/cm-1) 3362 (w), 2017 (m), 1902 (m), 1684
(s), 1653 (s), 1559 (m), 1036 (m). HR-MS Calcd for C19H22N2O2:
310.1681; Found: 310.1682.
3-Benzylamino-2-phenyl-2,3-dihydro-1-isoindol-1-one (6j). 1H
NMR (400 MHz, CDCl3) δ 2.51 (s, 1H, NH), 3.15 (d, 1H, -CH2-, J
) 12.9 Hz), 3.32 (d, 1H, -CH2-, J ) 12.9 Hz), 6.13 (s, 1H, CH-
Supporting Information Available: X-ray crystallographic
data for indene derivative 3f (PDF). This material is available
free of charge via the Internet at http://pubs.acs.org.
JA054216I
9
J. AM. CHEM. SOC. VOL. 128, NO. 1, 2006 209